RESUMO
BACKGROUND: Latin America has a high prevalence of Helicobacter pylori in children that may lead to peptic ulcer disease and eventually gastric cancer in adulthood. Successful eradication is hindered by rising antimicrobial resistance. We summarize H. pylori resistance rates in Latin American children from 2008 to 2023. MATERIAL AND METHODS: Systematic review following PRISMA guidelines and National Heart, Lung, and Blood Institute checklist to assess risk of bias (PROSPERO CRD42024517108) that included original cross-sectional observational studies reporting resistance to commonly used antibiotics in Latin American children and adolescents. We searched in PubMed, LILACS, and SciELO databases. RESULTS: Of 51 studies, 45 were excluded. The quality of the six analyzed studies (297 H. pylori-positive samples) was satisfactory. Phenotypic methods (N = 3) reported higher resistance rates than genotypic studies (N = 3). Clarithromycin resistance ranged from 8.0% to 26.7% (6 studies; 297 samples), metronidazole from 1.9% to 40.2% (4 studies; 211 samples), amoxicillin from 0% to 10.4% (3 studies; 158 samples), tetracycline resistance was not detected (3 studies; 158 samples), and levofloxacin resistance was 2.8% (1 study; 36 samples). CONCLUSION: Scarce Latin American studies on H. pylori resistance, along with methodological heterogeneity, hinder conclusive findings. Clarithromycin and metronidazole (first-line drugs) resistance is worrisome, likely impacting lower eradication rates. Urgent systematic surveillance or individual testing before treatment is necessary to enhance eradication.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , América Latina/epidemiologia , Adolescente , Criança , Antibacterianos/farmacologia , Pré-Escolar , Testes de Sensibilidade Microbiana , Estudos TransversaisRESUMO
Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here, we show that human intestinal vimentin+CD90+smooth muscle actin- SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn's disease SCs (Crohn's SCs), however, synthesized markedly less RA than SCs from healthy intestine (normal SCs). We also show that microbe-stimulated Crohn's SCs, which are more inflammatory than stimulated normal SCs, induced less RA-regulated differentiation of mucosal dendritic cells (DCs) (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory interferon-γhi/interleukin-17hi T cells than normal SCs. Explaining these results, Crohn's SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal and, thus, synthesized less RA than normal SCs. These findings uncover a microbe-SC-DC crosstalk in which luminal microbes induce Crohn's disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.
RESUMO
BACKGROUND: The urea breath test (UBT-13C) is a non-invasive technique that allows the diagnosis and confirmation of eradication of Helicobacter pylori infection. Aim: To evaluate H. pylori positivity and values of UBT-13C among infected Chilean children and adults, and to analyze its variation in relation to sex, nutritional status, and age of the patients. Material and Methods: Retrospective study of 1141 patients aged 6 to 94 years, with an indication for a UBT-13C either for diagnosis or for confirmation of eradication of H. pylori infection. 13C enrichment was measured using an infrared spectrometer calculating the delta 13C values before and after the ingestion of 13C marked urea. The clinical data of the patients were obtained at the time of the examination. Results: We included 241 children and 900 adults. Infected children obtained lower UBT-13C delta values than infected adults (16.1 ± 8.7 and 37 ± 52.9, respectively). The rates of infection were higher in males who were recruited for diagnosis. Significant differences were obtained between positivity for H. pylori in overweight and obese children but not adults. UBT-13C titers were significantly associated with the body mass index (BMI) only in adults. Conclusions: H. pylori infection rates are similar between sexes and are higher in children probably because of selection bias. In children, H. pylori positivity is associated with higher BMI and excess malnutrition although with similar UBT-13C values. In adults, H. pylori infection is not related with BMI, but a higher BMI impacts UBT-13C titers.
ANTECEDENTES: La prueba de aliento con urea (UBT-13C) es una técnica no invasiva que permite el diagnóstico y confirmación de erradicación de la infección por Helicobacter pylori. Objetivo: Evaluar los valores de UBT- 13C en niños y adultos chilenos infectados y analizar su variación en relación al sexo, diagnóstico nutricional y edad de los pacientes. Material y Métodos: Estudio retrospectivo de 1.141 pacientes de 6 a 94 años. El enriquecimiento de13C se midió usando un espectrómetro de infrarrojos, calculando el delta 13C antes y después de la ingesta de urea marcada con 13C. Los datos clínicos de los pacientes se obtuvieron al momento del examen. Resultados: Incluimos 241 niños y 900 adultos con valores delta de UBT-13C de 16,1 ± 8,7 frente a 37 ± 52,9, respectivamente. Las tasas de infección fueron mayores en los hombres reclutados para el diagnóstico. Se obtuvieron diferencias significativas entre la positividad para H. pylori en niños con sobrepeso y obesidad, pero no en adultos. Los títulos de UBT-13C se asociaron significativamente con el índice de masa corporal (IMC) solo en adultos. Conclusiones: Las tasas de infección por H. pylori son similares entre los sexos y aumentan en los niños probablemente debido al sesgo de selección. En niños, la positividad para H. pylori se asocia con un IMC más alto y malnutrición por exceso, aunque con valores similares de UBT-13C. En los adultos, la infección por H. pylori no se relaciona con el IMC ni con la obesidad, pero el aumento del IMC afecta los títulos de UBT-13C.
Assuntos
Humanos , Feminino , Helicobacter pylori , Infecções por Helicobacter/diagnóstico , Obesidade Infantil , Ureia , Testes Respiratórios , Isótopos de Carbono , Índice de Massa Corporal , Criança , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Transplante de Fígado , Tacrolimo/administração & dosagem , Ciclosporina/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagem , Fatores de Tempo , Fatores de Transcrição/imunologia , Esquema de Medicação , Linfócitos T/imunologia , Distribuição de Qui-Quadrado , Razão de Chances , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Transplante de Fígado/efeitos adversos , Resultado do Tratamento , Tacrolimo/efeitos adversos , Monitoramento de Medicamentos/métodos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Inibidores de Calcineurina , Rejeição de Enxerto/imunologia , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Ácido Micofenólico/efeitos adversosRESUMO
Durante la última década, con la aparición de técnicas de secuenciación de última generación basadas en la filogenia del gen ARN ribosomal 16S y complejas plataformas bioinformáticas, la composición del microbioma y su rol en salud y enfermedad ha sido sujeto de investigación activa. Existe una evidencia creciente que relaciona la disbiosis microbiana y un aumento del riesgo de desarrollar enfermedades de tipo inflamatorio, autoinmune, y metabólico tales como asma, diabetes, obesidad y enfermedades gastrointestinales crónicas. El ensamblaje de la microbiota intestinal en los humanos comienza antes y durante el proceso de parto y evoluciona con la alimentación durante la infancia y debe ser entendido en profunda relación con el microbioma de su madre. La comprensión del impacto de la microbiota en la morbilidad en seres humanos necesariamente requiere de una etapa previa como es el conocimiento del desarrollo y ensamblaje precoz de la microbiota en recién nacidos, y como las intervenciones médicas como la elección en la ruta de parto (parto cesárea versus parto vaginal), uso precoz de antibióticos, selección de fórmula láctea (lactancia materna versus fórmulas artificiales), entre otros, pueden modificar en forma sustancial su conformación y a través de cambios en el desarrollo del sistema inmune, ejercer un impacto en salud y enfermedad en neonatos, lactantes y posteriormente a lo largo de la vida de un ser humano.(AU)
In the last years, with the development of massive last generation sequencing techniques based on the phylogeny of 16S rRNA gene and complex bioinformatics platforms, the composition of the human microbiome and its role in health and disease has been an active subject of research. There is growing evidence that associate the intestinal disbiosis with an increase risk to develop chronic inflammatory, autoimmune, and metabolic diseases such as asthma, diabetes, obesity and chronic gastrointestinal conditions. The assembly of the intestinal microbiome in human begins before and during the birth process, progressing with the feeding duringm infancy and it must be understood in a close relationship with the microbiome of their mothers. The comprehension of the impact of microbiome in human morbidity will require of a previous stage, the knowledge of the development and early assembly of the microbiome in newborns, and to understand how early medical intervention such as delivery route (C-section versus vaginal delivery), early use and abuse of antibiotics, selection of formula patterns (human milk versus formula bottle milk) among others, may substantially modify the microbiome conformation and to have a profound impact in the development of the immune system, affecting later in life the development of disease in neonates, infants and adults.(AU)